3a. MCI and AD (cortical dementia)

Question 1

What forms of dementia are there?

Answer 1

Alzheimer (55%)
Misced AD&VD (15%)
Vascular dementia (15%)
Dementia with Lewy Bodies & Frontotemporal dementia (10%)
Others (5%)

Question 2

Techniques used when diagnosing dementia

Why EEG?

Answer 2

To differentiate between different kinds of dementia, or between dementia and depression.

Question 3

Techniques used when diagnosing dementia

Why CSF?

Answer 3

We can find clues as tau pathology in this fluid, this is especially helpful in young people.

Question 4

Techniques used when diagnosing dementia

Why lab?

Answer 4

To rule out other causes of cognitive decline.

Question 5

What is a delirium?

Answer 5

A disturbance in attention and awareness with a sudden onset, compared to dementia that has a gradual onset. Important: it tends to fluctuate in severity during the day.

Question 6

What are 3 sources of evidence for a delirium?

Answer 6

1. Disturbance in cognition: memory, orientation, language, hallucinations
2. It cannot be explained by another neurocognitive disorder that also has a sudden onset (e.g. infarction, coma)
3. There should be evidence that the disturbance is a direct physiologic consequence of another medical condition, substance intoxication, toxin, etc.

Question 7

What is a MCD/MCI?

Answer 7

Mild Neurocognitive Disorder or Mild Cognitive Impairment = evidence of a modest cognitive decline in 1 or more cognitive domains, but important: it does not interfere with daily functioning.

Question 8

What is the most pronounced decline in Amnestic MCI? (2 domains)

Answer 8

1. Memory: short term and delayed recall, flat learning curve.
2. EF: slowing, but intact comprehension.

Question 9

What the morphology of MCI?

Answer 9

Medial temporal lobe (entorhinal cortex & hippocampus) > atrophy on group level, on individual level the atrophy is less specific.

Question 10

What is a dementia?

Answer 10

Evidence of significant cognitive decline in 1 or more cognitive domains, which interferes with daily functioning.

Question 11

What are 2 histopathological changes in Alzheimer?

Answer 11

1. Accumulation of amyloid bèta: between te neurons in the medial temporal lobe
2. Abrogation of tau pathology: in the neurons (neurofibrillary tangles)

Question 12

NINCDS-ADRDA criteria for AD

What are 2 statements related to ‘Probable AD’?

Answer 12

1. Case of a dementia with an insidious onset (months/years) and a clear-cut history of worsening, with initial and prominent cognitive deficits in memory, language, EF, or visuospatial ability.
2. The level of certainty increases with follow-ups and with a genetic mutation.

Question 13

NINCDS-ADRDA criteria for AD

What are 3 statements related to ‘Improbable AD’?

Answer 13

1. Acute onset (e.g. delirium)
2. Focal neurological signs that start together with the cognitive decline (e.g. hemiparesis, visual field disturbances). AD doesn’t start with motor dysfunction!
3. Seizure or gait disturbances in early stages (e.g. brain tumor)

Question 14

NINCDS-ADRDA criteria for AD

What are 2 statements related to ‘Possible AD’?

Answer 14

1. Insufficient history: no family/friends, forgetful/confused
2. Mixed presentation: e.g. concomitant cerebrovascular disease, hallucinations as in DLB, or medication that can also cause the cognitive changes.

Question 15

Which 2 genes are associated with AD?

Answer 15

1. APP gene: encodes for the amyloid precursor protein > if a mutation, this leads to a wrong cleavage > wrong structure of amyloid > accumulation.
2. PSEN gene: also wrong processes in the brain > tissue loss.

Question 16

Which people have a higher change on developing AD? (3x)

And which genes/factors are associated here?

Answer 16

1. Trisomia 21: people with Down
2. Comorbidity: people with Parkinson
3. APOE 4 risk factor: Asian people (but not everyone with this risk factor develops AD)

Question 17

What domains are most pronounced in a NPA in AD patients? (6x)

Explain the domains.

Answer 17

1. (Episodic) memory
2. Orientation
3. Visuoconstruction
4. EF
5. Language
6. Behavioral/psychological symptoms
7. Short term more effected than the past, delayed recall is much worse, and also flat learning curves
8. Problems with orientation in time and place, and later also in person
9. Problems with construction and copying in later stages
10. Slowing, fluency, perseveration, disinhibition, compromised comprehension
11. Word finding and naming problems (already in the beginning)
12. Delusions, hallucinations, apathy/impulsivity, depression/euphoria, anxiety/fearlessness, agitation/aggression

Question 18

What does ‘Closing in’ mean and in what dementia is it seen?

Answer 18

When copying an image, they draw within the figure. You can see this in people with AD, and for example not in depressed people.

Question 19

Biomarkers of AD

What can be seen in PET?

Answer 19

Amyloid bèta deposition (more red in AD)

and

Tempoparietal hypometabolism (characterized by decreased brain glucose consumption) on F-fluorodeoxyglucose PET.

Question 20

Biomarkers of AD

What can be seen in CSF?

Answer 20

Reduced levels of amyloid bèta and elevated levels of phosphorylated tau and total tau in the CSF.

Question 21

Biomarkers of AD

What can be seen in MRI?

Answer 21

Medial temporal lobe atrophy (MTA) > hippocampus

MTA-0 means no tissue loss, MTA-4 means hippocampus almost gone.

Also atrophy in the rest of the brain, in younger people mostly in the parietal part.

Question 22

Biomarkers of AD

What can be seen in EEG?

Answer 22

Not expensive, easy to perform.

In an EEG you can differentiate between depression or different types of dementia (in AD more of the slower brain waves)

Question 23

EEG in AD

Which brain waves are increased and which brain waves are decreased?

Answer 23

Increased

• Theta activity (larger waves)
• In later stages also Delta activity (largest waves)

Decreased

• Alpha acivity (smaller)
• Bèta activity (smaller)